Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy.
The aim of the current study was to determine the frequency of mutations in the beta-myosin heavy chain gene (MYH7) in a cohort of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and their families, and to investigate correlations between genotype and phenotype. About 130 consecutive patients diagnosed with HCM or DCM (69 with HCM and 61 with DCM) attending the cardiology clinic of Post Graduate Institute of Medical Education and Research were screened for mutations in the MYH7 gene. The control group for genetic studies consisted of 100 healthy subjects. We report 14 mutations in 6 probands (5 probands in HCM and 1 proband in DCM) and their family members. Out of these 6 mutations, 3 are new and are being reported for the first time. One known mutation (p.Gly716Arg) was found to be "de novo" which resulted in severe asymmetric septal hypertrophy (31 mm) and resulted in the sudden cardiac death (SCD) of the proband at the age of 21 years. Further, a DCM causing novel mutation p.Gly377Ser was identified which resulted in the milder phenotype. The present study shows that there is genetic and phenotypic heterogeneity of cardiomyopathies in Indian population. Further, the location and type of mutation in a given sarcomeric gene determines the severity and phenotypic plasticity in cardiomyopathies.
Rai
Taranjit Singh
TS
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Ahmad
Shamim
S
Bahl
Ajay
A
Ahuja
Monica
M
Ahluwalia
Tarunveer Singh
TS
Singh
Balvinder
B
Talwar
K K
KK
Khullar
Madhu
M
D000328:Adult; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
C501641:MYH7 protein, human; D024722:Cardiac Myosins; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains